pre-miRNA Information | |
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pre-miRNA | hsa-mir-210 |
Genomic Coordinates | chr11: 568089 - 568198 |
Synonyms | MIRN210, mir-210, MIR210 |
Description | Homo sapiens miR-210 stem-loop |
Comment | This human miRNA was predicted by computational methods using conservation with mouse and Fugu rubripes sequences . |
RNA Secondary Structure | ![]() |
Associated Diseases | ![]() |
Mature miRNA Information | ||||||||||||||||||||||||||||||||||||||||
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Mature miRNA | hsa-miR-210-3p | |||||||||||||||||||||||||||||||||||||||
Sequence | 66| CUGUGCGUGUGACAGCGGCUGA |87 | |||||||||||||||||||||||||||||||||||||||
Evidence | Experimental | |||||||||||||||||||||||||||||||||||||||
Experiments | Cloned | |||||||||||||||||||||||||||||||||||||||
Editing Events in miRNAs |
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SNPs in miRNA |
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Putative Targets |
miRNA Expression profile | |
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Human miRNA Tissue Atlas | |
miRNAs in Extracellular Vesicles |
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Circulating MicroRNA Expression Profiling |
Biomarker Information |
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Gene Information | |||||||||||||||||||||
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Gene Symbol | CNTNAP5 | ||||||||||||||||||||
Synonyms | caspr5 | ||||||||||||||||||||
Description | contactin associated protein like 5 | ||||||||||||||||||||
Transcript | NM_130773 | ||||||||||||||||||||
Expression | |||||||||||||||||||||
Putative miRNA Targets on CNTNAP5 | |||||||||||||||||||||
3'UTR of CNTNAP5 (miRNA target sites are highlighted) |
>CNTNAP5|NM_130773|3'UTR 1 GAAACTGCAGGGTTCCTACTACTCTTTTTTCTTGTTGTTCAATTATCTCCTCCCCCTCTTCTCTCCTGTCTTTTGATTTG 81 GTCATTCTCTTTATTTTCTGCTTGCCATGTCTTTTCTGGAACATACTTGCATCCACCACAGCATCAATTCCCTTGATCCA 161 GCCCAAGAGACCAGGCAGCCATGGCCACTGCCTTCCTCTCTGATGAACCTATCGGGTGAAAACGACCACTCAAGAGACTG 241 ACTTCGCCATTCAAGACAAGGAAGAGACACATGTGTGCACTCCTGCATGTTCAGTTCTGTACTTCCAGTTTCTAAAATGC 321 ACTGTTCAGTTTTCCAACCACTTGGTGGTTCAGGCTTGCTTTGAACCTGAGCTCTTAGGCACATGACGGTCATTCCTGAC 401 ATCCTCCCCAGCTCAAGTCTATTCTTACCATAGAACCCAGGGCAGGGAGAGAAGAACCTAGAGGCCTGGTTTGCTTTGGT 481 GGCATTGTAAAAAGAGTAAGAGAGGTTTGGTTTGTGGTGGTTTGCTTTCTTTACCATAAGCAATCCCTTGCCTTAACTCA 561 TCACCCTTTTTCACTATGACCCTTAGACCCTGAGTATTTTCAAATATATGATTGCTGATAGTAGTGACCAAAACTACTTT 641 GTTCCTTTCTTACCACTCTCTCCTGGGGCCGACACGTTGGGACAGCACACCATAGCATAAAGCTAGGGGATGCATGGAAA 721 TAGCAGCTTGAAACTAGGAGGTAACAAGAAAGCTTCTAGGAAGTAGATGTTCCATATCTTCAAAATGCCTCCTCCAATTT 801 TGTAAGAATGCTAGCTAGGTATTCCTGGGATTATTATACTGAGATATATATATATACACACACACACACATATGTGTATA 881 TATGTATATATATATGTGAGTATATATACACACACACACACACACACACATATATATATATACACACACGCACACATATA 961 TGTTGCTGCAGCATAAAGAAATTGAAATAAAAGTTTAAAATAGTACCCGGTTCAATGAAAGAGCCTAAACCATCTTAACT 1041 CAGCTTTAAAACAAAAATTAAATCAGGAAAAAATGAAAAAAAAACTGCAAA Target sites
Provided by authors
Predicted by miRanda
DRVs
SNPs
DRVs & SNPs
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miRNA-target interactions (Predicted by miRanda) |
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DRVs in gene 3'UTRs | |||||||||||||||||||||
SNPs in gene 3'UTRs |
Experimental Support 1 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | HEK293 |
Disease | 129684.0 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
"HITS-CLIP data was present in GSM714642. RNA binding protein: AGO2. Condition:completeT1
"PAR-CLIP data was present in GSM714644. RNA binding protein: AGO2. Condition:completeT1
... - Kishore S; Jaskiewicz L; Burger L; Hausser et al., 2011, Nature methods. |
Article |
- Kishore S; Jaskiewicz L; Burger L; Hausser et al. - Nature methods, 2011
Cross-linking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins. We developed a method for CLIP data analysis, and applied it to compare CLIP with photoactivatable ribonucleoside-enhanced CLIP (PAR-CLIP) and to uncover how differences in cross-linking and ribonuclease digestion affect the identified sites. We found only small differences in accuracies of these methods in identifying binding sites of HuR, which binds low-complexity sequences, and Argonaute 2, which has a complex binding specificity. We found that cross-link-induced mutations led to single-nucleotide resolution for both PAR-CLIP and CLIP. Our results confirm the expectation from original CLIP publications that RNA-binding proteins do not protect their binding sites sufficiently under the denaturing conditions used during the CLIP procedure, and we show that extensive digestion with sequence-specific RNases strongly biases the recovered binding sites. This bias can be substantially reduced by milder nuclease digestion conditions.
LinkOut: [PMID: 21572407]
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Experimental Support 2 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | HEK293 |
Disease | 129684.0 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
"PAR-CLIP data was present in GSM1065667. RNA binding protein: AGO1. Condition:4-thiouridine
... - Memczak S; Jens M; Elefsinioti A; Torti F; et al., 2013, Nature. |
Article |
- Memczak S; Jens M; Elefsinioti A; Torti F; et al. - Nature, 2013
Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.
LinkOut: [PMID: 23446348]
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CLIP-seq Support 1 for dataset GSM714642 | |
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Method / RBP | HITS-CLIP / AGO2 |
Cell line / Condition | HEK293 / completeT1, repA |
Location of target site | ENST00000431078.1 | 3UTR | ACACACACACACACAUAUAUAUAUAUACACACACGCAC |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 21572407 / GSE28865 |
CLIP-seq Viewer | Link |
CLIP-seq Support 2 for dataset GSM714644 | |
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Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | HEK293 / completeT1, repA |
Location of target site | ENST00000431078.1 | 3UTR | AUAUACACACACACACACACACACACAUAUAUAUAUAUACACACACGCACACAUAUAU |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 21572407 / GSE28865 |
CLIP-seq Viewer | Link |
CLIP-seq Support 3 for dataset GSM1065667 | |
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Method / RBP | PAR-CLIP / AGO1 |
Cell line / Condition | HEK293 / 4-thiouridine, ML_MM_6 |
Location of target site | ENST00000431078.1 | 3UTR | CACACACACACACAUAUAUAUAUAUACACACAC |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 23446348 / GSE43573 |
CLIP-seq Viewer | Link |
MiRNA-Target Expression Profile | |||||||
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MiRNA-Target Expression Profile (TCGA) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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126 hsa-miR-210-3p Target Genes:
Functional analysis:
ID![]() |
Target | Description | Validation methods |
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Strong evidence | Less strong evidence | |||||||||||
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MIRT000149 | HOXA9 | homeobox A9 | ![]() |
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4 | 1 | ||||
MIRT000150 | TP53I11 | tumor protein p53 inducible protein 11 | ![]() |
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2 | 1 | ||||||
MIRT000151 | PIM1 | Pim-1 proto-oncogene, serine/threonine kinase | ![]() |
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2 | 1 | ||||||
MIRT000152 | HOXA1 | homeobox A1 | ![]() |
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2 | 1 | ||||||
MIRT000153 | FGFRL1 | fibroblast growth factor receptor like 1 | ![]() |
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6 | 3 | ||
MIRT000156 | RAD52 | RAD52 homolog, DNA repair protein | ![]() |
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5 | 3 | |||
MIRT001930 | NPTX1 | neuronal pentraxin 1 | ![]() |
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3 | 2 | |||||
MIRT002024 | EFNA3 | ephrin A3 | ![]() |
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8 | 8 | ||||||
MIRT003153 | BDNF | brain derived neurotrophic factor | ![]() |
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5 | 1 | |||
MIRT003154 | PTPN1 | protein tyrosine phosphatase, non-receptor type 1 | ![]() |
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5 | 1 | |||
MIRT003155 | P4HB | prolyl 4-hydroxylase subunit beta | ![]() |
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6 | 2 | ||||||
MIRT003156 | UBQLN1 | ubiquilin 1 | ![]() |
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3 | 1 | |||||
MIRT003157 | SERTAD2 | SERTA domain containing 2 | ![]() |
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3 | 1 | |||||
MIRT003158 | SEH1L | SEH1 like nucleoporin | ![]() |
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3 | 1 | |||||
MIRT003159 | NCAM1 | neural cell adhesion molecule 1 | ![]() |
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4 | 1 | ||||
MIRT003160 | MID1IP1 | MID1 interacting protein 1 | ![]() |
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3 | 1 | |||||
MIRT003161 | MDGA1 | MAM domain containing glycosylphosphatidylinositol anchor 1 | ![]() |
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3 | 1 | |||||
MIRT003162 | KIAA1161 | myogenesis regulating glycosidase (putative) | ![]() |
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3 | 1 | |||||
MIRT003163 | ISCU | iron-sulfur cluster assembly enzyme | ![]() |
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6 | 7 | ||
MIRT003164 | HOXA3 | homeobox A3 | ![]() |
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3 | 1 | |||||
MIRT003165 | GPD1L | glycerol-3-phosphate dehydrogenase 1 like | ![]() |
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7 | 2 | |||||
MIRT003166 | DENND6A | DENN domain containing 6A | ![]() |
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3 | 1 | |||||
MIRT003167 | CPEB2 | cytoplasmic polyadenylation element binding protein 2 | ![]() |
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5 | 1 | |||
MIRT003168 | CDK10 | cyclin dependent kinase 10 | ![]() |
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3 | 1 | |||||
MIRT003169 | ABCB9 | ATP binding cassette subfamily B member 9 | ![]() |
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3 | 1 | |||||
MIRT003170 | CBX1 | chromobox 1 | ![]() |
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3 | 1 | |||||
MIRT003171 | XIST | X inactive specific transcript (non-protein coding) | ![]() |
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4 | 1 | ||||
MIRT003172 | TNPO1 | transportin 1 | ![]() |
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3 | 1 | |||||
MIRT003173 | SMCHD1 | structural maintenance of chromosomes flexible hinge domain containing 1 | ![]() |
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3 | 1 | |||||
MIRT003174 | PTAR1 | protein prenyltransferase alpha subunit repeat containing 1 | ![]() |
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3 | 1 | |||||
MIRT003175 | NIPBL | NIPBL, cohesin loading factor | ![]() |
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3 | 1 | |||||
MIRT003176 | MIB1 | mindbomb E3 ubiquitin protein ligase 1 | ![]() |
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3 | 1 | |||||
MIRT003177 | HECTD1 | HECT domain E3 ubiquitin protein ligase 1 | ![]() |
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3 | 1 | |||||
MIRT003178 | ELK3 | ELK3, ETS transcription factor | ![]() |
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3 | 1 | |||||
MIRT003179 | DDAH1 | dimethylarginine dimethylaminohydrolase 1 | ![]() |
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4 | 1 | ||||
MIRT003180 | CLASP2 | cytoplasmic linker associated protein 2 | ![]() |
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3 | 1 | |||||
MIRT003181 | CHD9 | chromodomain helicase DNA binding protein 9 | ![]() |
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3 | 1 | |||||
MIRT003182 | ATP11C | ATPase phospholipid transporting 11C | ![]() |
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3 | 1 | |||||
MIRT003183 | APC | APC, WNT signaling pathway regulator | ![]() |
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3 | 1 | |||||
MIRT003184 | E2F3 | E2F transcription factor 3 | ![]() |
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7 | 5 | |||||
MIRT003185 | ACVR1B | activin A receptor type 1B | ![]() |
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2 | 1 | ||||||
MIRT003916 | MRE11A | MRE11 homolog, double strand break repair nuclease | ![]() |
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2 | 1 | ||||||
MIRT003917 | XPA | XPA, DNA damage recognition and repair factor | ![]() |
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2 | 1 | ||||||
MIRT004672 | MNT | MAX network transcriptional repressor | ![]() |
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4 | 2 | ||||
MIRT006326 | AIFM3 | apoptosis inducing factor, mitochondria associated 3 | ![]() |
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3 | 2 | |||||
MIRT006519 | CASP8AP2 | caspase 8 associated protein 2 | ![]() |
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4 | 1 | ||||
MIRT006663 | VMP1 | vacuole membrane protein 1 | ![]() |
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3 | 2 | |||||
MIRT006830 | TFRC | transferrin receptor | ![]() |
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3 | 2 | |||||
MIRT047002 | PFDN2 | prefoldin subunit 2 | ![]() |
1 | 1 | |||||||
MIRT047003 | U2AF2 | U2 small nuclear RNA auxiliary factor 2 | ![]() |
1 | 1 | |||||||
MIRT047004 | UBA1 | ubiquitin like modifier activating enzyme 1 | ![]() |
1 | 1 | |||||||
MIRT047005 | ESPL1 | extra spindle pole bodies like 1, separase | ![]() |
1 | 1 | |||||||
MIRT047006 | ACTR1A | ARP1 actin related protein 1 homolog A | ![]() |
1 | 1 | |||||||
MIRT047007 | SCN1B | sodium voltage-gated channel beta subunit 1 | ![]() |
1 | 1 | |||||||
MIRT047008 | RCC2 | regulator of chromosome condensation 2 | ![]() |
1 | 1 | |||||||
MIRT053179 | HSD17B1 | hydroxysteroid 17-beta dehydrogenase 1 | ![]() |
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2 | 1 | ||||||
MIRT054098 | NDUFA4 | NDUFA4, mitochondrial complex associated | ![]() |
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4 | 2 | ||||
MIRT054099 | SDHD | succinate dehydrogenase complex subunit D | ![]() |
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6 | 4 | ||
MIRT054141 | STMN1 | stathmin 1 | ![]() |
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3 | 1 | |||||
MIRT054142 | DIMT1L | DIM1 dimethyladenosine transferase 1 homolog | ![]() |
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4 | 2 | ||||
MIRT054186 | ROD1 | polypyrimidine tract binding protein 3 | ![]() |
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3 | 1 | |||||
MIRT054203 | ALDH5A1 | aldehyde dehydrogenase 5 family member A1 | ![]() |
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4 | 1 | ||||
MIRT054204 | FOXN3 | forkhead box N3 | ![]() |
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5 | 2 | |||
MIRT054205 | MCM3 | minichromosome maintenance complex component 3 | ![]() |
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4 | 1 | ||||
MIRT054206 | IGFBP3 | insulin like growth factor binding protein 3 | ![]() |
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6 | 2 | ||||||
MIRT054207 | COL4A2 | collagen type IV alpha 2 chain | ![]() |
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6 | 2 | ||||||
MIRT054208 | INPP5A | inositol polyphosphate-5-phosphatase A | ![]() |
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4 | 1 | ||||
MIRT054209 | EHD2 | EH domain containing 2 | ![]() |
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4 | 1 | ||||
MIRT054210 | SH3BGRL | SH3 domain binding glutamate rich protein like | ![]() |
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5 | 2 | |||
MIRT054248 | PTPN2 | protein tyrosine phosphatase, non-receptor type 2 | ![]() |
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3 | 1 | |||||
MIRT054321 | LDHA | lactate dehydrogenase A | ![]() |
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2 | 1 | ||||||
MIRT054324 | LDHB | lactate dehydrogenase B | ![]() |
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2 | 1 | ||||||
MIRT054349 | HIF1A | hypoxia inducible factor 1 alpha subunit | ![]() |
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5 | 2 | |||||
MIRT054714 | FOXP3 | forkhead box P3 | ![]() |
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3 | 1 | |||||
MIRT054794 | HIF3A | hypoxia inducible factor 3 alpha subunit | ![]() |
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3 | 1 | |||||
MIRT115688 | MGRN1 | mahogunin ring finger 1 | ![]() |
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2 | 3 | ||||||
MIRT170674 | INSIG1 | insulin induced gene 1 | ![]() |
1 | 1 | |||||||
MIRT437785 | BNIP3 | BCL2 interacting protein 3 | ![]() |
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5 | 2 | |||||
MIRT438739 | KCMF1 | potassium channel modulatory factor 1 | ![]() |
1 | 1 | |||||||
MIRT439407 | TNPO3 | transportin 3 | ![]() |
1 | 1 | |||||||
MIRT439629 | SIPA1L3 | signal induced proliferation associated 1 like 3 | ![]() |
1 | 1 | |||||||
MIRT439632 | SIN3A | SIN3 transcription regulator family member A | ![]() |
1 | 1 | |||||||
MIRT439740 | RPL22 | ribosomal protein L22 | ![]() |
1 | 1 | |||||||
MIRT439886 | PSAP | prosaposin | ![]() |
1 | 1 | |||||||
MIRT439918 | PPP1R2 | protein phosphatase 1 regulatory inhibitor subunit 2 | ![]() |
1 | 1 | |||||||
MIRT439928 | POU2AF1 | POU class 2 associating factor 1 | ![]() |
1 | 1 | |||||||
MIRT440033 | ICMT | isoprenylcysteine carboxyl methyltransferase | ![]() |
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2 | 3 | ||||||
MIRT440255 | MEF2D | myocyte enhancer factor 2D | ![]() |
1 | 1 | |||||||
MIRT440491 | HMGCS1 | 3-hydroxy-3-methylglutaryl-CoA synthase 1 | ![]() |
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2 | 3 | ||||||
MIRT440570 | GIT2 | GIT ArfGAP 2 | ![]() |
1 | 1 | |||||||
MIRT440647 | FCHSD2 | FCH and double SH3 domains 2 | ![]() |
1 | 1 | |||||||
MIRT440830 | DEAF1 | DEAF1, transcription factor | ![]() |
1 | 1 | |||||||
MIRT440866 | CSNK1E | casein kinase 1 epsilon | ![]() |
1 | 1 | |||||||
MIRT472232 | NFIC | nuclear factor I C | ![]() |
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2 | 2 | ||||||
MIRT473190 | MITF | melanogenesis associated transcription factor | ![]() |
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2 | 2 | ||||||
MIRT477856 | DYRK2 | dual specificity tyrosine phosphorylation regulated kinase 2 | ![]() |
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2 | 2 | ||||||
MIRT497528 | ZNF607 | zinc finger protein 607 | ![]() |
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2 | 2 | ||||||
MIRT509770 | SERTM1 | serine rich and transmembrane domain containing 1 | ![]() |
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2 | 6 | ||||||
MIRT524407 | CNTNAP5 | contactin associated protein like 5 | ![]() |
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2 | 4 | ||||||
MIRT535209 | PKIA | cAMP-dependent protein kinase inhibitor alpha | ![]() |
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2 | 4 | ||||||
MIRT554511 | RUNX1T1 | RUNX1 translocation partner 1 | ![]() |
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2 | 4 | ||||||
MIRT558069 | ESCO2 | establishment of sister chromatid cohesion N-acetyltransferase 2 | ![]() |
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2 | 2 | ||||||
MIRT572273 | KCNJ6 | potassium voltage-gated channel subfamily J member 6 | ![]() |
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2 | 2 | ||||||
MIRT574255 | DOCK7 | dedicator of cytokinesis 7 | ![]() |
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2 | 4 | ||||||
MIRT575621 | Foxn3 | forkhead box N3 | ![]() |
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2 | 2 | ||||||
MIRT575742 | Zfp618 | zinc finger protein 618 | ![]() |
1 | 1 | |||||||
MIRT609050 | VAMP4 | vesicle associated membrane protein 4 | ![]() |
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2 | 2 | ||||||
MIRT611143 | TNRC6B | trinucleotide repeat containing 6B | ![]() |
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2 | 4 | ||||||
MIRT699226 | SLCO3A1 | solute carrier organic anion transporter family member 3A1 | ![]() |
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2 | 2 | ||||||
MIRT703060 | GTDC1 | glycosyltransferase like domain containing 1 | ![]() |
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2 | 2 | ||||||
MIRT716005 | ASB11 | ankyrin repeat and SOCS box containing 11 | ![]() |
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2 | 2 | ||||||
MIRT731682 | BTK | Bruton tyrosine kinase | ![]() |
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3 | 1 | |||||
MIRT733090 | DLEU2L | deleted in lymphocytic leukemia 2-like | ![]() |
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3 | 0 | |||||
MIRT733091 | BRCA2 | BRCA2, DNA repair associated | ![]() |
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3 | 0 | |||||
MIRT733156 | ITGA5 | integrin subunit alpha 5 | ![]() |
1 | 0 | |||||||
MIRT733501 | GATA1 | GATA binding protein 1 | ![]() |
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3 | 0 | |||||
MIRT733503 | SMAD2 | SMAD family member 2 | ![]() |
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3 | 0 | |||||
MIRT733525 | MIR210HG | MIR210 host gene | ![]() |
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2 | 0 | ||||||
MIRT733615 | TGFBI | transforming growth factor beta induced | ![]() |
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2 | 0 | ||||||
MIRT734175 | KRAS | KRAS proto-oncogene, GTPase | ![]() |
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2 | 0 | ||||||
MIRT734293 | PTEN | phosphatase and tensin homolog | ![]() |
1 | 0 | |||||||
MIRT734568 | STAT6 | signal transducer and activator of transcription 6 | ![]() |
1 | 0 | |||||||
MIRT734966 | ADAMTS6 | ADAM metallopeptidase with thrombospondin type 1 motif 6 | ![]() |
1 | 0 | |||||||
MIRT736294 | ID2 | inhibitor of DNA binding 2, HLH protein | ![]() |
1 | 0 | |||||||
MIRT737104 | FABP4 | fatty acid binding protein 4, adipocyte | ![]() |
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3 | 0 | |||||
MIRT756028 | NTN4 | netrin 4 | 3 | 1 |
miRNA-Drug Associations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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miRNA-Drug Resistance Associations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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